RESUMEN
We performed a retrospective review of standard anteroposterior and lateral radiographs of the thumb in 80 patients, to compare two radiographic landmarks, in terms of mediolateral bone support, for centering the trapezial component in total joint arthroplasty. On anteroposterior view, we identified the distal articular surface of the trapezium and trapezium width, and defined the two midpoints as radiographic landmarks for positioning a 9-mm trapezial cup. Mean trapezium width was significantly greater than the distal articular surface of the trapezium, and the midpoints did not match. Thus, after positioning simulated 9-mm prosthetic cups centered on each landmark, the residual radial bone distance was significantly greater using the landmark based on trapezium width. The mean value was 33% greater with this landmark, and the minimum value was 2.1 mm, compared to 0.2 mm using the landmark based on the distal articular surface. Our study thus suggested that the midpoint of the trapezium width is the more relevant radiographic landmark for centering the trapezial prosthetic cup in total joint arthroplasty, by preserving better bone stock on the radial side without depleting the ulnar side. On an intraoperative anteroposterior fluoroscopic view, this landmark could be used to check cup positioning.
Asunto(s)
Hueso Trapecio , Artroplastia , Humanos , Radiografía , Radio (Anatomía)/cirugía , Pulgar/cirugía , Hueso Trapecio/diagnóstico por imagen , Hueso Trapecio/cirugíaRESUMEN
BACKGROUND: Fingolimod (FTY720) has previously shown clinical efficacy in phase II/III studies of predominantly Caucasian populations with multiple sclerosis (MS). OBJECTIVES: To report six-month efficacy and safety outcomes in Japanese patients with relapsing MS treated with fingolimod. METHODS: In this double-blind, parallel-group, phase II study, 171 Japanese patients with relapsing MS were randomized to receive once-daily fingolimod 0.5 mg or 1.25 mg, or matching placebo for six months. The primary and secondary endpoints were the percentages of patients free from gadolinium (Gd)-enhanced lesions at months 3 and 6, and relapses over six months, respectively; safety outcomes were also assessed. RESULTS: 147 patients completed the study. Higher proportions of patients were free from Gd-enhanced lesions at months 3 and 6 with fingolimod (0.5 mg: 70%, p = 0.004; 1.25 mg: 86%, p < 0.001) than with placebo (40%). Odds ratios for the proportions of relapse-free patients over six months favoured fingolimod versus placebo but were not significant. Adverse events related to fingolimod included transient bradycardia and atrioventricular block at treatment initiation, and elevated liver enzyme levels. CONCLUSIONS: This study demonstrated the clinical efficacy of fingolimod for the first time in Japanese patients with MS, consistent with the established effects of fingolimod in Caucasian patients.
Asunto(s)
Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Glicoles de Propileno/uso terapéutico , Esfingosina/análogos & derivados , Adolescente , Adulto , Pueblo Asiatico , Método Doble Ciego , Esquema de Medicación , Femenino , Clorhidrato de Fingolimod , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Japón/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/etnología , Oportunidad Relativa , Glicoles de Propileno/administración & dosificación , Glicoles de Propileno/efectos adversos , Recurrencia , Esfingosina/administración & dosificación , Esfingosina/efectos adversos , Esfingosina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Safety issues in biotechnology are subject to considerable controversy in public debate. Public concern is focused in particular on the degree of uncertainty associated with inadvertent and unforeseeable impacts of the deliberate or accidental release of genetically engineered organisms into the environment. The objective of this article is to demonstrate that there is a factual, scientific basis to environmental safety issues, by means of which the real, case-specific hazards requiring serious consideration by scientists, representatives of regulatory agencies and the public can be distinguished from conjectural hazards and naturally occurring background processes.
Asunto(s)
Biotecnología/tendencias , Ambiente , Contención de Riesgos Biológicos , Salud Ambiental , Ingeniería Genética/efectos adversos , Humanos , Medición de Riesgo , SeguridadRESUMEN
Yeasts degrade glucose through different metabolic pathways, where the choice of the pathway is dependent on the nature of the limitation in the various substrates. When oxygen is limiting in addition to glucose, yeasts often grow according to a mixture of oxidative and reductive metabolism. Oxygen may be limiting either by supply or by inherent biological restrictions such as the respiratory bottleneck in Saccharomyces cerevisiae or by both. A unified model incorporating both supply and biological limitations is proposed for the quantitative prediction of growth rates, consumption and production rates, as well as key metabolite concentrations during mixed oxidoreductive metabolism occurring as a result of such oxygen limitations. This simple unstructured model can be applied to different yeast strains while at the same time requiring a minimum number of measured parameters. "Estimators" are utilized in order to predict the presence of supply-side or biological limitations. The values of these estimators also characterize the relative importance of oxidative to total metabolism. Results from the aerobic and oxygen-limited chemostat cultures were used to corroborate the model predictions. During these experiments, the heat released by the yeast cultures was also monitored on-line. The model correctly predicted the overall stoichiometry, steady-state concentrations, and rates including heat dissipation rates measured in the various situations of oxygen limitations. Direct continuous measurements such as heat can be used in conjunction with the unified model for on-line process control.
RESUMEN
Fundamental aspects of chemostat cultures are reviewed. Using yeast cultures as examples, it is shown that steady states in chemostats may be predicted quantitatively by combining the correct number of unstructured kinetic models with expressions for existing stoichiometric constraints. The necessary number of such kinetic models corresponds to the number of limiting substrates and increases with the number of different metabolic pathways available to the strain. This is demonstrated by an experimental comparison of yeast growth limited by glucose alone for which metabolism is oxidative, and growth doubly limited by both glucose and oxygen, which occurs according to an oxido-reductive metabolism. The steady state data for such experiments can in principle be predicted based on a minimal amount of information by a simple stoichiometric model. It represents the overall stoichiometry of growth by a superposition of a fully oxidative and a fully reductive growth reaction and uses the concept of "aerobicity" to characterize the relative importance of the two reactions.
Asunto(s)
Kluyveromyces/crecimiento & desarrollo , Micología/métodos , Saccharomyces cerevisiae/crecimiento & desarrollo , Aerobiosis , Biotecnología/métodos , Cinética , Matemática , Modelos Teóricos , Consumo de OxígenoRESUMEN
The growth physiology of Saccharomyces cerevisiae strains H1022 and Whi2+ has been studied in aerobic batch and continuous (chemostat) cultures. Results from the measurement of biomass and medium components (off-line) together with oxygen, carbon dioxide and heat measurements (on-line) have been used in an attempt to explore the existence of 'overflow' or 'bottleneck' metabolism as opposed to catabolite repression (Crabtree effect) in these strains. Chemostat experiments indicated that specific oxygen uptake rate (qO2) was linearly related to the dilution rate (D) at values below the critical dilution rate (D crit), becoming constant above D crit, which is in agreement with the bottleneck theory. However, batch culture experiments indicated negligible oxygen consumption during the initial glucose growth phase, the culture exhibiting purely anaerobic metabolism. The bottleneck theory would propose that qO2 has a constant (maximum) value under these conditions. The results presented here suggest that while the bottleneck theory can be adequately used to describe chemostat growth of S. cerevisiae, some other control mechanism must be operating under conditions of high glucose concentrations, such as those initially prevailing in the batch culture experiments.